To the Editor: Dr Cummings and colleagues1 reported that measurement of serum estradiol levels
in older postmenopausal women by sensitive radioimmunoassay (RIA) identified
those at high risk of breast cancer, who may benefit most from raloxifene
treatment. Although the authors claim to have used a highly sensitive estradiol
RIA, they provide virtually no information about its reliability. Direct estradiol
immunoassays are generally considered to be unreliable for quantifying very
low estradiol levels because they lack sensitivity and specificity to measure
these levels accurately.2 This is because
direct immunoassays for steroid hormones are generally carried out with commercial
reagents (sold as kits) that are used in a fixed assay method without purification
of the analyte. The methods typically require a small aliquot of sample, generally
0.1 to 0.2 mL. Thus, a highly sensitive standard curve is required to quantify
reliably very low levels of an analyte in such small sample volumes. In contrast,
in RIA methods with preceding purification steps, relatively larger serum
sample volumes of 1.0 to 1.5 mL can be used. This flexibility in aliquot volume
does not require a highly sensitive standard curve and allows low concentrations
of an analyte to be measured in a more accurate portion of the standard curve.